title: Mitochondrial dysfunction and transactivation of p53-dependent apoptotic genes in BaP-treated human fetal lung fibroblasts.
abstract: Benzo(a)pyrene (BaP) has been shown to be an inducer of apoptosis. However, mechanisms involved in BaP-induced mitochondrial dysfunction are not well-known. In this study, human fetal lung fibroblasts cells were treated with BaP (8, 16, 32, 64 and 128 μM) for 4 and 12 h. Cell viability, intracellular level of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), mitochondrial membrane potential (ΔΨ(m)) and cytochrome c release were determined. Changes in transcriptional levels of p53-dependent apoptotic genes (p53, APAF1, CASPASE3, CASPASE9, NOXA and PUMA) were measured. At time point of 4 h, BaP induced the intracellular ROS generation in 64 (p < .05) and 128 μM BaP groups (p < .01) but decreased the T-AOC activities in 32, 64 (p < .05 for both) and 128 μM BaP groups (p < .01). At time point of 12 h, ΔΨ(m) significantly decreased in ≥32 μM BaP groups (p < .05 for all). Amount of mitochondrial cytochrome c significantly increased in 128 μM BaP group (p < .01). Transcriptional levels of CASPASE3, CASPASE9, APAF1 and PUMA were up-regulated in all BaP groups (p < .05 for all) and in ≥32 μM groups for NOXA (p < .05). But only in 16 μM BaP group a relatively little expression of p53 mRNA was observed (p < .05). The results indicate that in the earlier period BaP promoted the generation of excessive ROS and subsequently the mitochondrial depolarization, whereas transactivations of the p53-dependent apoptotic genes were significantly induced at the later period.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guangtao
authors.initials: G
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Kaimin
authors.initials: K
authors.lastname: Rao
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ailin
authors.initials: A
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000196:embryology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D028361:Mitochondrial Diseases / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002273:Carcinogens; D017382:Reactive Oxygen Species; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene; D045304:Cytochromes c